The calcium ion binding and phospholipid binding behavior of prothrombin necessary for optimal rates of thrombin production in the blood coagulation process depend on the presence of gamma-carboxyglutamic acid (Gla) residues. This vitamin K-dependent amino acid is located at ten positions within the first 33 residues of prothromibin and at similar positions in the other vitamin K-dependent coagulation proteins factors VII, IX, X and Protein C. A related gamma-carboxyglutamix-containing region also occurs in bone proteins. We suggest that the 1-40 region of prothrombin, containing the 18-23 cystine loop, is critical to the functional behavior of prothrombin as well as related structures of the other vitamin K-dependent coagulation factors and perhaps other proteins, such as the bone protein, containing Gla and a similar cystine loop. We intend to prepare segments of the 1-40 region by chemical synthesis; we will also utilize the peptides representing the 1-39 and 12-44 sequences obtained from prothrombin. We intend to establish; (a) the chemical structure of the smallest unit of the amino terminal region of prothrombin that will exhibit the metal ion-induced characteristics of the protein; (b) the role of the cystine loop; (c) the nature of the ligand system in the Gla region that is required for metal ion binding; and, (d) the minimum number and location of Gla residues in the 1-33 sequence necessary for prothrombin-phospholipid interaction. Experimental techniques that will be employed to study the chemical and physical properties of these synthetic and natural peptides include nuclear magnetic resonance, laser Raman and Emu3+ luminescence spectroscopy; metal ion binding; interaction with antibodies specific to the calcium ion-induced conformation; and peptide; solvent and peptide:lipid partition experiments. A method for chemical modification of Gla residues is also proposed.